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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3951-3959. Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-11-3763. This Article Full Text (PDF) All Versions of this Article: 2003-11-3763v1 103/10/3951    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chai, J.-G. Articles by Scott, D. Search for Related Content PubMed PubMed Citation Articles by Chai, J.-G. Articles by Scott, D. Social Bookmarking                   What's this? Submitted November 5, 2003 Accepted January 5, 2004 Transplantation tolerance induced by intranasal administration of HY peptides Jian-Guo Chai, Edward James, Hamlata Dewchand, Elizabeth Simpson, and Diane Scott* Transplantation Biology Group, MRC Clinical Sciences Centre, Imperial College, London, Hammersmith Campus, London, United Kingdom * Corresponding author; email: diane.scott{at}csc.mrc.ac.uk. Induction of antigen specific tolerance to transplantation antigens is desirable to control host-versus-graft and graft-versus-host reactions. Following molecular identification of a set of minor histocompatibility (H) antigens, we have used selected HY peptide epitopes for this purpose. Intranasal administration of individual MHC class II restricted HY peptides induces indefinite survival of syngeneic male skin grafts and allows engraftment of male bone marrow. Tolerance involves linked suppression to additional HY epitopes on test grafts. Long-term tolerance also requires suppression of emerging thymic emigrants. It does not involve deletion: HY peptide specific CD4+ and CD8+ T cells expand on re-exposure to male antigen; these expansions are smaller in tolerant than control mice and fewer HY-specific cells from tolerant females secrete IFN and IL10. Significantly, CD4+ cells from peptide pre-treated females fail to make IL2 responses to cognate peptide, limiting expansion of the HY specific CD8+ populations that can cause graft rejection. Consistent with this, tolerance induction by HY peptide is abrogated by co-administration of LPS. IL10 does not appear to be critically involved, since tolerance is inducible in IL10 deficient mice. Adoptive transfer of tolerance into naive neonatal recipients by splenocytes from long-term tolerant donors provides evidence for involvement of regulatory cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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